Method of Reducing the Occurrence of Arrhythmias Via Photobiomodulation and Apparatus for Same

ABSTRACT

In response to local or systemic inflammation in a patient, photobiomodulation therapy is applied to a cardiac location to reduce the risk and/or occurrence of cardiac arrhythmia. Once inflammation is identified, photobiomodulation therapy can be applied in any suitable fashion (e.g., via a catheter- or transesophageal probe-mounted photoemitter, via an externally-applied photoemitter, or via photoemitter incorporated into an implantable medical device). Photobiomodulation therapy can also be employed to good advantage in conjunction with non-photobiomodulation therapy (e.g., traditional cardiac rhythm management therapies).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/933,112, filed 5 Nov. 2015, now pending, which is a divisional ofU.S. application Ser. No. 13/047,983, filed 15 Mar. 2011, now U.S. Pat.No. 9,180,307. The forgoing applications are hereby incorporated byreference in their entirety as though fully set forth herein.

BACKGROUND OF THE INVENTION

a. Field of the Invention

The instant invention relates generally to the reduction and preventionof arrhythmias, such as atrial fibrillation. More specifically, theinstant invention relates to apparatus and methods for reducing andpreventing arrhythmias using photobiomodulation therapy, either alone orin conjunction with other therapies.

b. Background Art

In photobiomodulation therapy, laser light is applied to tissue in orderto address an abnormal tissue response. In general, photobiomodulationcan be described as the use of light to induce a biological response inliving cells and tissue as a direct result of the absorbance of light bythe living cells and tissue.

One widespread and widely accepted use of photobiomodulation therapy isfor the reduction of pain. For example, photobiomodulation has beenshown to reduce pain associated with acute inflammation, for exampleresulting from acute ankle sprains, acute Achilles tendonitis, and oralsurgery. In these circumstances, photobiomodulation therapy is presumedto exert anti-inflammatory effects, for example by reducing the levelsof prostaglandin E₂, tumor necrosis factor-α, and interleukin-1.

It is widely accepted that some of the effects of photobiomodulation areexerted through interaction between the laser light and an enzyme,cytochrome c oxidase, present in mitochondria. This enzyme functions asa photoacceptor for light of certain wavelengths. After absorption oflight, energy transfer occurs. Cytochrome c oxidase is the last enzymein the cellular respiratory chain and is crucial for the formation ofATP which, in turn, provides energy for biochemical processes such asmuscle contraction and metabolic reactions. For example, larger numbersof non-damaged mitochondria as well as higher levels of ATP have beenobserved in the ischemic zone after myocardial infarction in animalstreated with photobiomodulation therapy as compared to untreatedanimals.

Atrial fibrillation is one of the most common cardiac arrhythmias,affecting millions of people worldwide. The economic stress of atrialfibrillation on the health care system is enormous, and, as the westernpopulation grows older, the number of atrial fibrillation patients ispredicted to rise.

It is known that atrial fibrillation results from disorganizedelectrical activity in the heart muscle (the myocardium). The underlyingcauses of atrial fibrillation, however, are not completely understood,though it is understood that hypertensive patients are at a higher riskof developing atrial fibrillation.

It is also known that angiotensin II causes inflammation and vice versa.Further, the induction of atrial fibrosis is angiotensin II dependent,and atrial fibrosis is thought to be one of the mechanisms causingatrial fibrillation. Indeed, human atrial tissue expression ofangiotensin II receptors have been linked with increased cell death andleukocyte infiltration. This may demonstrate a potential link betweenthe renin-angiotensin-aldosterone system (“RAAS”), inflammation, andatrial fibrillation. As known, RAAS inhibition has desirable effects,both in primary and secondary prevention of atrial fibrillation.

BRIEF SUMMARY OF THE INVENTION

The inventors thus suspect that inflammation of cardiac tissue plays arole in the initiation of certain arrhythmias, such as atrialfibrillation. Photobiomodulation therapy is useful in the reduction ofinflammation. Accordingly, it is an object of the present invention toprevent and reduce atrial fibrillation by addressing cardiacinflammation via the application of, inter alia, photobiomodulationtherapy.

Disclosed herein is a method of reducing the occurrence of cardiacarrhythmia, including the steps of: identifying inflammation indicativeof a risk of cardiac arrhythmia in a patient; and applyingphotobiomodulation therapy to a cardiac location in order to reduce alikelihood of a cardiac arrhythmia. The inflammation may be systemic orlocal and, if local, may be either local to cardiac tissue or otherwise.The photobiomodulation therapy desirably utilizes light having awavelength between about 600 nm and about 1100 nm, and can optionally beprovided in conjunction with non-photobiomodulation therapy (e.g.,cardiac pacing).

The photobiomodulation therapy can be applied in a number of differentways. For example, in one aspect, a catheter having a photoemitter isnavigated through a patient's vasculature to a position proximate thecardiac location and then the photoemitter is activated to deliverphotobiomodulation therapy to the inflamed cardiac location.

In another aspect, a photoemitter is positioned on an exterior surfaceof a patient's body proximate the cardiac location and activated todeliver photobiomodulation therapy to the inflamed cardiac location.

In still another aspect, a transesophageal probe having a photoemitteris deployed to a location proximate the cardiac location via a patient'sesophagus. The photoemitter is then activated to deliverphotobiomodulation therapy to the inflamed cardiac location.

In yet another aspect, a medical device including a photoemitter isimplanted at a location proximate the cardiac location, and thephotoemitter is activated to deliver photobiomodulation therapy to theinflamed cardiac location.

Optionally, at least one physiologic characteristic is monitored, andactivation of the photoemitter to deliver photobiomodulation therapy isresponsive to the monitored at least one physiologic characteristic.Suitable physiologic characteristics include, but are not limited to,pressures and myocardial wall accelerations. The photoemitter may alsobe activated to deliver photobiomodulation therapy “on demand” (e.g.,responsive to a patient's input) or according to a prescribed orpreselected treatment schedule.

It is also contemplated that the implanted medical device can include,in addition to a photoemitter, a lead operable in at least one of acardiac sensing mode and a cardiac pacing mode. In such embodiments, theactivation of the photoemitter to deliver photobiomodulation therapy canbe responsive to a signal received by the lead operating in a cardiacsensing mode.

Also disclosed herein is a medical device for implantation into acardiac tissue in order to reduce occurrence of cardiac arrhythmias. Thedevice includes a photoemitter configured to deliver photobiomodulationtherapy to the cardiac tissue; and at least one of a sensor to monitor aphysiologic characteristic and a therapy delivery element to deliver anon-photobiomodulation therapy to the cardiac tissue. The sensor tomonitor a physiologic characteristic can be a pressure sensor, anaccelerometer, or any other device suitable for use in measuringphysiological characteristics.

The photoemitter can be an optical fiber coupled to a light source, alitroenergic material, or any other device suitable for delivering lightof an appropriate wavelength and intensity to tissue.

The foregoing and other aspects, features, details, utilities, andadvantages of the present invention will be apparent from reading thefollowing description and claims, and from reviewing the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates a photoemitter deployed into the right atrium of apatient's heart via the patient's vasculature.

FIG. 1B also illustrates a photoemitter deployed into the right atriumof a patient's heart via the patient's vasculature.

FIG. 2 depicts a photoemitter for the external application ofphotobiomodulation therapy.

FIG. 3 depicts a photoemitter deployed transesophageally.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides apparatus and methods for preventing andreducing the occurrence of cardiac arrhythmias, such as atrialfibrillation, through the application of, inter alia, photobiomodulationtherapy to inflamed cardiac tissue. Though the present invention will bedescribed in the context of preventing and reducing the occurrence ofcardiac arrhythmias, it is contemplated that the teachings herein can bepracticed to good advantage in other settings as well. For example,photobiomodulation therapy as described herein may also be practiced inconjunction with spinal cord stimulation, vagal nerve stimulation,gastric stimulation, or any other therapy delivered via an implantablepulse generator.

As described above, the inventors theorize that there is a link betweencardiac inflammation and the risk of developing cardiac arrhythmia.Thus, methods of preventing and reducing the occurrence of cardiacarrhythmias according to the present invention include identifyinginflammation that is indicative of a risk of a patient developingcardiac arrhythmia. For purposes of this disclosure, inflammation refersnot only to local inflammation, but also to systemic inflammation.

As described above, there is a relationship between angiotensin II andinflammation. Thus, when there is a systemic inflammatory state in asubject, there may also be increased levels of angiotensin II in theblood. Because angiotensin II acts as a pro-inflammatory molecule, theincreased level of angiotensin may, in turn, lead to local inflammationin cardiac tissue, thus increasing the risk of atrial fibrosis andatrial fibrillation. In other words, whether inflammation is systemic orlocal (to the heart or otherwise), the increased levels of angiotensinII will cause an increased risk for AF.

Systemic inflammation can be detected in various ways, such as throughanalysis of body temperature, blood samples, and IEGM. For example, thefollowing blood markers often indicate systemic inflammation: c-reactiveprotein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)and erythrocyte sedimentation rate. Similarly, Troponin T, troponin I,creatine kinase MB (CK-MB), and myoglobin are markers of myocardialdamage, while cystatin C is a marker of renal damage, which may occur atinflammation. In addition, angiotensin-converting enzyme can be measuredin blood as a marker of increased angiotensin II activity.

Once inflammation (systemic or local, to the heart or otherwise) hasbeen identified, photobiomodulation therapy can be applied in order toreduce local inflammation in cardiac tissue (e.g., ischemic ventricularregions, infarct ventricular regions). This, in turn, reduces thepatient's risk of developing an arrhythmia.

The present invention encompasses any number of methodologies ofdelivering photobiomodulation therapy to an inflamed cardiac location,which will be familiar to those of ordinary skill in the art. Forexample, United States patent application publication no. 2004/0260367,which is hereby incorporated by reference as though fully set forthherein, discloses delivery of photobiomodulation to a patient's heartvia an externally-applied device (in FIGS. 2A and 2B), via a catheter(in FIG. 12), and via a transesophageal probe (in FIGS. 11A and 11B).Similarly, PCT publication WO2008066423, which is hereby incorporated byreference as though fully set forth herein, discloses an implantablecardiac device that can also deliver phototherapy in order to facilitatethe healing process associated with device implantation.

Neither United States patent application publication no. 2004/0260367nor PCT publication WO2008066423, however, recognizes the beneficial,arrhythmia-reducing and arrhythmia-preventing effects ofphotobiomodulation therapy. Nonetheless, because various suitablemethods of delivering photobiomodulation therapy will be familiar tothose of ordinary skill in the art, these methodologies will only bedescribed herein to the extent necessary to understand the presentinvention.

FIGS. 1A and 1B illustrate a first method of deliveringphotobiomodulation therapy to an inflamed cardiac location. As shown inFIGS. 1A and 1B, a catheter 10 having a photoemitter 12 at a distal endthereof is navigated through the patient's vasculature to a positionproximate the inflamed cardiac location. For the sake of illustration,catheter 10 is shown as being introduced into the patient's right atriumvia the superior vena cava. It should be understood, of course, thatcatheter 10 may be navigated through the patient's vasculature, usingany suitable known technique (e.g., steerable catheters, non-steerablecatheters introduced through steerable introducer sheaths, cathetersintroduced over guidewires, and the like), into any cardiac chamberwithout departing from the spirit and scope of the present invention.

FIG. 2 depicts a second method of delivering photobiomodulation therapyto an inflamed cardiac location. As shown in FIG. 2, a photoemitter 12is positioned on an exterior surface of the patient's body proximate theinflamed cardiac location and activated to emit light, therebydelivering photobiomodulation therapy to the inflamed cardiac location.Such externally-applied photobiomodulation therapy has the advantage ofbeing completely non-invasive, but may not be as effective asinternally-applied (e.g., catheter-delivered) photobiomodulationtherapy. In addition, though FIG. 2 depicts the patient on anexamination table, it should be understood that photoemitter 12 may beprovided as part of or on a belt or other wearable device that permitsthe patient to stand, and even move about, while undergoingphotobiomodulation therapy.

FIG. 3 depicts a third method of delivering photobiomodulation therapyto an inflamed cardiac location. As shown in FIG. 3, a photoemitter 12is positioned on a transesophageal probe 14. Probe 14 is introduced, viathe patient's esophagus, to a location proximate the inflamed cardiaclocation, and photoemitter 12 is activated to deliver photobiomodulationtherapy thereto. One of ordinary skill in the art will appreciate thatthis method of delivering photobiomodulation therapy is slightly lessinvasive than catheter-delivered photobiomodulation therapy and likelyto be more effective than externally-applied photobiomodulation therapy.

Photoemitter 12 may include any suitable light source, as generallyknown in the photobiomodulation art. For example, in some embodiments ofthe invention, photoemitter 12 includes one or more optical fiberscoupled to one or more light sources. In the embodiment of the inventiondepicted in FIGS. 1A and 1B, the optical fibers (and any lenses used inconnection therewith) are connected to catheter 10 so as to be carriedby catheter 10 through the patient's vasculature. Likewise, in theembodiment of the invention depicted in FIG. 3, the optical fibers (andany lenses used in connection therewith) are connected to probe 14 so asto be carried by probe 14 through the patient's esophagus. Typically,the light source will remain outside the patient's body, but it iswithin the scope of the invention to provide a light source that issufficiently small to be incorporated into catheter 10 or probe 14 alongwith the optical fiber assembly.

In other embodiments of the invention, photoemitter 12 may include alitroenergic material. Litroenergic materials are materials that emitlight continuously without an external power source. Suitablelitroenergic materials include LITROSPHERES·, manufactured by MPK Co. ofClayton, Wisconsin. Such materials can be molded into and/or paintedonto the distal end of catheter 10, probe 14, or another suitabledevice.

Typically, the light used in photobiomodulation therapy deliveredaccording to the teachings herein will have a wavelength of betweenabout 600 nm and about 1100 nm. Of course, these wavelengths are merelyexemplary, and other wavelengths could be employed, if deemed beneficialto the patient, without departing from the spirit and scope of thepresent invention.

In some embodiments of the invention, one or more medical devicesrespectively including one or more photoemitters are implanted into apatient at locations proximate inflamed cardiac locations. Methods ofimplantation of such medical devices are generally known, for example inconnection with the implantation of cardiac pacing leads.

An implanted photoemitter can be activated as necessary or desirable inorder to prevent and reduce the occurrence of cardiac arrhythmia,without necessitating a catheterization procedure every timephotobiomodulation therapy is to be delivered. Photoemitter implantationmay be desirable where a preselected treatment schedule calls forphotobiomodulation therapy to be delivered over an extended period oftime, such as every other day for two weeks.

Photoemitter implantation may also be advantageous wherephotobiomodulation therapy is delivered “on demand” by the patient. Forexample, if the patient experiences symptoms of hypertension, which maybe a precursor to cardiac arrhythmia, the patient can activate thephotoemitter in order to reduce or prevent the occurrence of anarrhythmia, similar to how a patient might take a nitroglycerin pillwhen experiencing symptoms of angina.

It is also contemplated to incorporate one or more photoemitters into animplantable cardiac pacing lead, such as a cardiac resynchronizationtherapy (CRT), cardiac resynchronization therapy defibrillator (CRT-D),implantable cardioverter-defibrillator (ICD), or brady device. Such aconfiguration advantageously provides a single device capable ofdelivering both traditional cardiac rhythm management therapy andphotobiomodulation therapy.

An implanted medical device including a photoemitter may additionally,or alternatively, include a sensor (e.g., a sensing lead) to enablemonitoring of one or more physiologic characteristics. A control systemcan be established that activates the photoemitter in response to themonitored physiologic characteristics.

As one example, the photoemitter can be coupled to a pressure sensor,such as the HeartPOD™ implantable heart failure therapy system, whichmeasures a patient's left atrial pressure. As another example, thephotoemitter can be coupled to a sensor that measures atrial wallstress. As yet another example, the photoemitter can be coupled to anaccelerometer that measures the acceleration of the atrial wall. Othersuitable sensors include motion sensors, position sensors, and sensorsfor measuring cardiac electrograms.

The control system can, in response to measurements made by the sensoror sensors, activate the photoemitter as appropriate in order to preventor reduce the occurrence of a cardiac arrhythmia. For example, in thecase where the sensor measures cardiac electrograms, the control systemcan activate the photoemitter when an irregular electrogram is detected.

Although several embodiments of this invention have been described abovewith a certain degree of particularity, those skilled in the art couldmake numerous alterations to the disclosed embodiments without departingfrom the spirit or scope of this invention. For example, one of ordinaryskill in the art will readily appreciate that photobiomodulation therapycan be delivered according to any suitable schedule using any suitablewavelength of light.

As another example, it should be understood that sensors used as part ofa control system for the delivery of photobiomodulation therapy need notbe implanted, and may be external to the patient. For example, ratherthan using an internal cardiac sensing lead, the photoemitter may becoupled to the output of a Holter monitor.

As still another example, the non-photobiomodulation therapy is notlimited to traditional cardiac rhythm management therapy, and includes,for example, pharmacologic therapy, ablation therapy, surgicaltherapies, and the like.

All directional references (e.g., upper, lower, upward, downward, left,right, leftward, rightward, top, bottom, above, below, vertical,horizontal, clockwise, and counterclockwise) are only used foridentification purposes to aid the reader's understanding of the presentinvention, and do not create limitations, particularly as to theposition, orientation, or use of the invention. Joinder references(e.g., attached, coupled, connected, and the like) are to be construedbroadly and may include intermediate members between a connection ofelements and relative movement between elements. As such, joinderreferences do not necessarily infer that two elements are directlyconnected and in fixed relation to each other.

It is intended that all matter contained in the above description orshown in the accompanying drawings shall be interpreted as illustrativeonly and not limiting. Changes in detail or structure may be madewithout departing from the spirit of the invention as defined in theappended claims.

1-20. (canceled)
 21. An apparatus for cardiovascular treatment,comprising: a photoemitter; and at least one of a sensor to monitor aphysiologic characteristic of a cardiovascular tissue and a therapydelivery element to deliver a non-photobiomodulation therapy to thecardiovascular tissue.
 22. The apparatus according to claim 21, whereinthe therapy delivery element comprises an ablation element.
 23. Theapparatus according to claim 21, further comprising an elongate body,and wherein the photoemitter is mounted to a distal portion of theelongate body.
 24. The apparatus according to claim 23, wherein theelongate body comprises a catheter.
 25. The apparatus according to claim23, wherein the elongate body comprises a transesophageal probe.
 26. Theapparatus according to claim 21, further comprising a control system,and wherein the control system is configured: to receive an input fromthe sensor; to detect, from the input, a physiologic characteristic ofthe cardiovascular tissue indicative of an arrhythmia risk; and toactivate the photoemitter to deliver photobiomodulation therapy to thecardiovascular tissue to mitigate the physiologic characteristicindicative of the arrhythmia risk.
 27. The apparatus according to claim26, wherein the physiologic characteristic indicative of the arrhythmiarisk comprises local inflammation of the cardiovascular tissue.
 28. Theapparatus according to claim 27, wherein the cardiovascular tissuecomprises cardiac tissue.
 29. An apparatus for cardiovascular treatment,comprising: a sensor to monitor a physiologic characteristic; aphotoemitter; and a control system that receives an output of the sensoras an input and that is configured to activate the photoemitter todeliver photobiomodulation therapy to a cardiovascular tissue inresponse to the output of the sensor.
 30. The apparatus according toclaim 29, further comprising an elongate body, and wherein thephotoemitter is carried by the elongate body.
 31. The apparatusaccording to claim 30, wherein the elongate body is one of a catheterand a transesophageal probe.
 32. The apparatus according to claim 29,wherein the physiologic characteristic comprises inflammation of thecardiovascular tissue.
 33. The apparatus according to claim 32, whereinthe cardiovascular tissue comprises cardiac tissue.
 34. The apparatusaccording to claim 29, further comprising a therapy delivery element todeliver a non-photobiomodulation therapy to the cardiovascular tissue.35. The apparatus according to claim 34, wherein the therapy deliveryelement comprises an ablation element.
 36. A method of cardiovasculartreatment, comprising: identifying a physiologic characteristicindicative of a risk of the patient developing a cardiovascularabnormality; and applying photobiomodulation therapy to a cardiovasculartissue in order to mitigate the physiologic characteristic and inhibitthe development of the cardiovascular abnormality.
 37. The methodaccording to claim 36, wherein: the cardiovascular abnormality comprisescardiac arrhythmia; and the physiologic characteristic comprisesinflammation of the cardiovascular tissue.
 38. The method according toclaim 37, wherein the cardiovascular tissue comprises cardiac tissue.39. The method according to claim 36, further comprising deliveringnon-photobiomodulation therapy to the cardiovascular tissue.
 40. Themethod according to claim 39, wherein delivering non-photobiomodulationtherapy to the cardiovascular tissue comprises ablating thecardiovascular tissue.